(l2)^#fl^1a*ftftlcs•:yL^T4.^ia*4^fc@^stfiffi
(43) S^^HB
2003 ^2 ^20 H (20.02.2003)
PCX
(10) Sfgi]^§IS-t
wo 03/014740 Al
(51) lUg^i^^^':
(25) m^mmonmi
(26) g[S^gB(;r)^t§:
COIN 33/543
PCT/JP02/08163
2002 ^8 fl9 a (09.08.2002)
(30) S5fe<tT-^:
!f#igl2001-242765 2001 ^8 ^ 9 B (09.08.2001) JP
(71) a3aAr*§*K^<±■c(7)^gg^lcol^r;: «^t®
^itS^^^ti: (MATSUSHITA ELECTRIC INDUS-
TRIAL CO., LTD.) [JP/JP]; T 571-8501 :*;BRJff PIKifJ
::*:¥Pia 1 O O 6 Osaka (JP).
(72) ^m%;tSJ;:XS
(75) 5§W%/tisilA r*§^-':5l^■ca)^;: lERI
(NADAOKA,Masataka) [JP/JP]; T 799-3113 S jfi
ff^rtr 8 1 9-5 Ehime (JP). SIS = ft
(TAKAHASHI,Mie) [JP/JP]; f 792-0026 ^
g/grfi ^SB90r2-1 3-1 Ehime (JP). ea*
(TANAKA,Hirotaka) [JP/JP]; T 791-1 102 ^Ul
m *tt»T 5 3 3-1-1 0 2 Ehime (JP). :ibfiS ICiK
(KJTAWAKI,Fumlhisa) [JP/JP]; =r 571-0064 :^B5Jfip PI
HrfT^^PT2 5-3 «i^^2 1 1 -^Osaka(JP).
(74) itmX: S- (HAYASE,Kenichi); =f532-0003 X
iT:*:IKe;n 3Pg^2g^#i^¥«iRSOsaka(jP).
(81) ft^g (^P^;: ON, JP, KR, US.
(84) figs (TStt;: 3 - □ »y / (AT, BE, BG. CH. CY,
CZ, DE, DK. EE, ES, FI, FR, GB, GR, IE, IT, LU, MC, NL,
PT, SE, SK, TR).
(54) Title: BIOSENSORS AND MEASUREMENT METHOD
(54) ^mo^^i /Utiii^v-s BLXfm^um
o
(57) Abstract: A biosensor provided with a development layer for developing a solution sample, and having a reagent part which
is immobilized on a part of the development layer and another reagent part which is held in a labeled and dry state on a part of
the development layer and can be eluted by developing the solution sample. By this biosensor, a component to be measured in the
solution sample is qualitatively or quantitatively measured by quantifying the bonded labeling reagent in the reagent immobilization
part In this biosensor, a prozone phenomenon can be detected by using a plural number of the reagent immobilization parts and
varying the aflflnities of the respective reagent immobilization parts for the subject to be measured in the solution sample or the
labeling reagent Also, a biosensor having a high measurement accuracy whereby the concentration of the subject to be measured
in the solution sample can be measured over a broadened dynamic range is provided. Thus, it is possible to provide a biosensor by
which a prozone phenomenon can be detected even in case of measuring a subject concentration over a wide range and which has a
wide <fynamic measurement range, a high precision and a high accuracy.
wo 03/014740 Al liliilliliniillliliiilliiilllliine
2S:1:=l-Kau^^terollSfSl;o^,^rl^. ^mmn^h^
{ST)
wo 03/014740
1
PCT/JP02/08163
m m m
5 ^ws^w
^m^is\^^x\i. B/FMmt'm^mm^'^^m^£^t\m\^x. Kst^Mxh^
wo 03/014740
PCT/JP02/08163
2
10 < J; 15 %muo%\^^mis^'m:}i 10-2745
;&fe^> #M¥l 0-2 7 4 6 5 3^<^#(c:^$n5. 7^-e®^i: UT^
15 -feV'f-r^-^^ ;^ J; !? Jtfi^^^^jtm^if LT. 3 0 0 5
3 0 3 -f-tC^ottS^PJ^^ mm^l- 1 5 9 3 9 Z%<biWm^. #^¥8 - 2 7
;55^^S^cWS.LTV^5o POCT^^:*3V^T^t. Ms ffiOEs ]E?it::pj^x*
wo 03/014740
PCT/JP02/08163
3
mmm^H. mB-^^^v^ y^^jt^mmi^. m^n^immm^^\'^m^iat
wo 03/014740
PCT/JP02/08163
4
wo 03/014740 PCT/JP02/08163
5
-25 mmm-^i^mi, ^\.<\t.m5M^^\^n^^miM^Wifi^^iix\ -fxiv
wo 03/014740
PCT/JP02/08163
6
wo 03/014740 PCT/JP02/08163
7 ■
wo 03/014740
PCT/JP02/08163
8
5 $ ^\mmti:m^. m^Pf^t:^<m^ Uj:\,^m\^m^o mnmmi^mm
15 mmm^^^wM-t^^^mhxmh±mmimm.ir^mmmmMim
20 ^lmv^Uf^ofBll^6^I©v^TtL^^^Ei^<7)/■^'i'^•fe>'f-^-*^v^T. mria
wo 03/014740
PCT/JP02/08163
9
wo 03/014740
10
PCT/JP02/08163
10 a^l OJ^cov^•ftl;^l^^cfEi4©^M:t-fe^/f-^c:*5V^T. iffiE^ms^'fbSP;^^ 2 ;&
15 H^l l^^^V^■fi^/0^^-iE«^^/W;t^r>'i^^^:*5V^T, BtfE^^<^i*^@^«
W^o^H^l l^(^v^-f;^^/&^^::is«©^^-r:^>'i^^cjo^^-c. iilB«g:(Df^:m
Xm]MJ7\^\Cyy( y^Xm^it^flXisy) , ^Oy-Om^s 0. 5mm~2.
±r'fo5 t ^<mt Lrz-h(Dxh y) > m^<D^m^ 1 ^^J^v^L»*(^OT^ 1
;fe-|6]»j:7'l'>'^t"@;t{b$tlT*5!9, -tOUipI^iS 0 . 5mm~2. Omml?2fe9s
wo 03/014740
PCT/JP02/08163
11
10 kmxh^:Lt^m^tLrch(Dxh^. wo^5ffl^lII?*£v^ut5^?(^
mm. Mxh^^ tiWi^ti-^h(7)X'h^o ^^x<D]kmtii. jk^^co^
^WWitt^h(DXh^o
mm^om^^^M^. hv<\tMm:r^. mm:}jWii:Ltc-hoxh^. mm
wo 03/014740
12
PCT/JP02/08163
imWi(Dm^(Dmn% \ 9 3ll5«(Z>^BJ(i, l»*cD^!i^l 7Jlt/c{if|^©
25 :^mm(Dm^<D^mm 2 1 TOttois^gfi, w^^^Hm 1 7:^7^d^v^ tit*©
wo 03/014740
PCT/JP02/081<>3
13
$tl-CV^5^:i:t>^C, y-(ymz^tiXti^. tmoy-f^^i^maiil. Omm&.
15 '^11^2 23I<DV^Ttb;6^^-B^(^S0S;^m^-*5V^T. #ilE«w|*^@fe'fb§P:J>
wo 03/014740
PCT/JP02/08163
14
(oi^^^m\^^v^\\ ^(o^M^(DmmmK mi^}:.m\(n>^m'^
if5jtot5H^2 4^(7:)V^m;6M^:fBi4(^SlJ^:^^^e:j3V^-c. BtfiE«o^^g^
25 Mm2 5:^©v^-ftL;^)^^:|B«^©SlJSj^^£^c*3V^T. MIBtei. WM^*^
wo 03/014740
PCT/JP02/08163
15
ami 031, »*(^M^l 2 3I;t^V^Lft*(D@|ffl^l 6^(7?V^-ftL;5M^lEi4<Z)
5 oT-fe "J > m^omm^ i Ln^comm^ i o m^ommm 1 2 ^^^jj
15 \zm-^mxtii)'^^%-%<. d>o,. 2#ss.i>*3#sme-t5i*ii@;t{b§i5o
tfc^jCDT-fct?, It*©®ll^l 7II/.^V^Uf*(D«m2 6
3iis«fe©/-<^ ^ffl v>T. ^^m&m\^^ ft 5 wrasisi^^<^3^-a^
wo 03/014740
PCT/JP02/08163
16
wo 03/014740
PCT/JP02/08163
17
wo 03/014740
18
PCT/JP02/08163
20 um^^ i-^yi^ uyi:?tm^j: 6ztx\ mfm^<DummMim\^is\, -^x. ^
25 ;^-feyi^^^*3V^T, t&IE^^@^{blf|5/55, ttflSlS^^^^t (^^iJJtM^^I. 1j L
wo 03/014740
PCT/JP02/08163
19
2 :t)mX'h^ :itX. mBmMM^^m&^^ i-^y^ uyiP:d^jX < . io:/
15 W^oOT^l 23SIS»o/M>j-fe>'1^^^:J;n{^. ft*<^^i£laml^^^v^LW
*<^«Sffl^l 13I<z?v^-ftL^4^:|S^(^/<^;^-fe:/^^^^:fcv^T. H«l5«o|*m@
7/V7D-^^-e&!9, WI5lite^«Jt«;6S. W«:^^W<^®W^|^
25 WUTSii:;^|B]|C7-Y V5l^t-C@;t^b$n-C*it), -?:(D7-f O. 5mm
~2. OmmT?fci9. ^bf-. «0|iSJ^@^MF^07>f>^Sgil;iS. 1. 0
mmmmt^m. M^^SW-^^:7^^!9J^t-V^i&S, o. 5mm~2. Omm^-r
wo 03/014740
PCT/JP02/08163
20
mi^<DmmM 1 4 ^(^/-^^ :t± yf - j; tiff, m^o^mf^ iw£\f^ tit
15 5o
wo 03/014740
PCT/JP02/08163
21
15 :55#Pjtt5„
m^<om.mm 2 0 ^sismwiss^^jfei;: i n^ommm 1 7 ^ v ^ Lit*
wo 03/014740
22
PCT/JP02/081<)3
aij^-c. >/-yw^-ts :i <b -c. J; «3 lEiittd^fii < . ^ ^ mM. mm.
wo 03/014740
PCT/JP02/08163
23
wo 03/014740
24
PCT/JP02/08163
15 PJ^:*rfe^^:^3v^T. |fri3 3:*Bf<^^Bia^<b^(7) 5 MiaftMSM^&l-
20
5 (a) H) , :^^B^O*5g(DMl(cjott5:/p/-^fijaiiig-|i| ims (b
wo 03/014740
PCT/JP02/08163
25
-(:t±>'^Mm (^6 (a) H) , :^^m<omm(Dmm2iLi&i-f^><y(:t-t:y
i)-^7^i-mm (^6 (b) m) .
10 ) ma, ^^mo-mmo^Bm^Trrr^u ^±y^Mmvh'o . mi (b) m
15 nm^^u n.m:mx\ mm^mmi!i^y)miii-^m^^mx\ ^m^mm^o
Mmymm^M-r^'^^x:^'^ h'mm.m^^WLxh^o 5, 9^tnmm^<m
m^^^mt(Dm-^m^m^x^^X7. ^mm.xm
20 ^'^b^l^-cv^5o ^bic, ^mm&imi (5) ^cfflv^5^<$:t.
n (9) xm\^mi$int. ^m^^m'^cDmmM^mi^ni-^m^umm^j:^
(omx'^t^K !^^-rL-h2:^mx'h^!i^mttj:<. 2:^msiJix$j^if, ^(on
wo 03/014740
PCT/JP02/08163
26
1-5 ^m±'r^if^t:Wtz'tfc-h<DXh^o :l^X(D
20 7 itmmm ^m^-t ^ ^^m tti>i^. stm. mm. m^j: mm(Dim^(D
ABs. yf^vmitt^=^/v^^ ^immumm. ^y^m.
wo 03/014740
PCT/JP02/08163
27
5 ^oalJJg*cov^Tm^ (b) mm^^xm-r^o mmmmt> wm
i-5#^(^f^s ^(o-^m&.±.(Di^m^im^-^^:itx!£^m[c!i^\:.xmM^m
wo 03/014740
PCT/JP02/08163
28
itmrmii^isn § mm 3 i,z.mmt^o ^» 3 ix tm^mm^y- v ib^t^: < m
-a-m ^t>i*^@^«n (9) t:-m&-t^^tx%hfi^. -^mim^'i^^
'bb<tt3£pi^MitTfe5ri:wtL<. mmimmmb\.x\t. led (l
25 i g h t Em i t t i n g Diode; |§3fej?''l' K) . LD (L a s e
r Diode; l^—f ^jj^-xf K) ^"M^CDjJi^gfCljS CTjI*^ pTfgT'fc
wo 03/014740
29
PCT/JP02/08163
) Mit, :^mm(DmM(Dmm2^^yu:t±>"^^mxh'o. (b) m
mmijim^^WLxh^o 5, 9. i4{i^m@
:5it;^@S{b^fpn. t^ms^-fbSpn^ir^L. ^^^^4'<^JB!J5t^
MI (5) iz.m^^mw-t, ^mmmtm o) , ^s:t;5i*»^«iii (1
4) xm^^im-wtit. ^^^mwpo-m^M^mi^Mi-m^mm^^^mi^^
25 {blfI5dS3:*B}f<^^J-C^-r/5^ Mt, mmMM(DmmiXm\^tc2:tjm<Dm^(D,
wo 03/014740
30
PCT/JP02/D8163
±(D^^ (D^mM^M±xi>m^^mt}xhi>m^^, zmmomtKDM
5ri:tt-95^-ct^£v\ mmm±.(^mm^^\^x\>. y^y-^xh^'^^m-ifs:
mz.i6n^mwmmM-&im\t^mmm^x\^^:htK ^nK^^^xh. &f\^
15 i ^im, p E Tr-7°r'«fi&$tLSo »sr^ 1 (c:^i^i-5aj^:s:i>% m
mm^mm(Dmm-m^^^%. mmm ^m^^mtm^^m-^ %(dx-^
^m^h<Df^m. m^±-r^\m^nfz^fch(oxh^, z.z.x(D^[-m^^
(Dt^^t\-i^ ^mMfi:wmmm(DWk'^s ^mMt^^fi}£xwMmmm^mk
m^imi (5) . mmm^itm o) . pmmMimm (i4) ^moM
mm^^^^mmt^n^xh^ib^h. {}>f£<kh. mm-^mts:^mt:mc^6
2^ . ^mmo:>T^:)f^[cMLxmfmm^mm^^^m^'^^mm^t^^t%x
i -ctt e & p E T 7 A ^ n ^ „ sts 7 itmrnm ^M^t-t 5 ^§0 ^i^o
wo 03/014740 PCT/JP02/08163
31
fnwm 8 fi. w^^^mm<D. t± y-t^m mo uk.
mo^m'^m^^ti^-to m^mm^ s a b s . ;k y ;^ ^ u -^'jmt
ii^ts m&^mmim^m\.xw^x^^. t.it. ^m^^mommimmt^
i|tt3iej^ST'f:i?^£V>o GiM^M^J) lOfi. »lrM-r
v-;\^<D^r/i^=i-;\^xhnm^^m^ttxh^o ^<Dm^ummn'm m
M^wm) mK±h.^mk^m^t\^xm\^'^^m^km\z
wo 03/014740
32
PCT/JPO2/08I63
it^(DMi,^}^sCx. mm^mmm (5) x^^^iifj:i3-otcmmKmu (4
10 ^(DAicft^]^x. mmmmm^imi (5) Rximmm^imE o) x-
15 mu3Kmm-^o mm^3\±, tm^mm^y- hn^^iKm^^nx^^^M.
20 «(DM^t/M^i^(i. piTkffic^^iisf^-K.^iiir-f, mM^-M^mzmm^
5o ^(-iJ^rlfi. MIE^^SSiblfP I (5) {djattS, ^w^c^^-a-jytti.
St/^@^«n (9) , l^mTOkOT (14) ^W1--5CtT'#bti'5o
wo 03/014740
PCT/JP02/0gl63
33
5 mtmitm^ty. mmnM^om;^. ^tcn. m^^mm\f^x. mm
ED (Light Emitting Diode ;^3fei5^^^-K) > LD (
Laser Diode; K) ^"^#(^■^^^^(^1^^ CTj14R
10 -^mxh^o i^tz^ mwmmm^&i (5) ^w.^^m^^(DBmn^wm^
^ffl^cfflv^r. nmm^it^n (9) , nmmMimm (14) Kisn^mmm
in.mmMii^.^tifcmimm'imi (5) , ^@s«n o) i:.
wo 03/014740
PCT/JP02/08W3
34
mmmm^\m»Lx 3 o'^mm^^m^tc, 3o^m. Tr i s-hci
mmmmmm^^mu lo'j^mm't^^m^tcw::^ morr i s-hci
10. • mmmmm^xm-i o^rm'^^^m'o , m(Dm^^nti:otco 2^m^^fT
^=ttiy( hit, 0. oi%m\:.^<Dm^'^<Dioovm^\!:.i%^:^y^m
?^^An;t 5 r i: J; o TM t fco 31^^ 3 0 ^P^li^ttfcmtc, MMMWiicXf^
15 mmi^. incRpmwc^iia^xmM^WLtcm^. phqcdi o%bsa
(^jkmr/i^zfs. y) ^^ftn 1 5»fc{t;!jDx.x»-t-'5 ^ t x\ mm
Sr4U 2ooooGT♦50:9■»L^^^fiti-^ri:{cj:o-c. nmmt^mi^
^tbir»M»it (i%BSA- y^^MW ^^mmLtcm^. mm^
Xs 0. 8 /im(D7^'/t'i?tc:xJijiLfc^Hl, S|J]W^=in^ KMSO, . 1 0
^<D 1 Step®! LT , 4 "cxBm Ltc. m^=i u }fmmiimmt:mmfiktii
m^itv^fyi, Rxj^mmty^ ynt^bmtitc. ^m^mmmmib:^^^)^^
wo 03/014740
PCT/JP02/08163
35
5 OmmXiii^O. 5 mm) ^«tfco mW-^rmfmithhib^Cibl . SMJw
10 b) m^(Dmm
^M^Mt LTEDTA • 2K^M^tcA(Dsk^^s ^^h^]) y hft4 5%
^ ^ O C R P ^^jfl^^M LfCo
c) ^i^;t±©Mfe;K^(Diaij^
15 :/f-f;itJVNr. TO^AlfPl^C R P 5 0 M 1 mjt^p L
WL%m\Wm^ J: !9 thii Lfc. ^n^M 2 mtd^-To ^ 2 llltt«0j(^-^jfeo
?^^te:4o}t5»iIl^^t> ^2|l(C*3tt§ 1 1 (±».^^U 6 3 5 nmCO^
20 mw u—f~xh^ . t.fc, mm 1 2 §^^^{±7 h ^-r ;t- k-c« $ tt
So ^hK. y<^^±iy-^iQm-^M^u nmm-^imi (5) , stmms
25 i^2:timxh^. m^w^^^m^mM-t^mim^n\^x±Mm\zM^ii<D-m
^*Mw^^mi.tzm^xh^x. mMm'^h^-^<DmMxh^^. %3m(D
wo 03/014740
36
PCT/JP02/08163
mmmtLX. 0. Img/dK 0. Smg/dK 1. Omg/
dU 3. Omg/d K 7. Omg/dl, 17. Omg/d K 3 7. Om
g/d K 8 0. Omg/d 1 ocRP^^^-r5^i^/V;^•feyi^^^:^Pt
r s^^a-s L/co # c R p m^(D!mi^nt?>^'^^ ^± i^f-±(^re® jfe-fklHso
5 ^mumm^mmmx^mMLtco ess nmjc^jjt^MS^ffsijLT.
n (9) ;5^b#btLfc@^3t^-cfe5o mt^hm^n. rnh^z^ crp^cmi-s
i^;^^yx;dWj:Sri:;5S;bj5^5o ^t::, (a) H^tJ^^s (b) ll(^ffiv^
15 U'^'J^^mB&llIlr^U ^5 (b) iltt:^^^©-^©JF^^tc*5ft57'ny-i^
^j^Wia^^-To ms (a) mix nm^m^^^Lrc^^^(Dmmmxh^o
^5 (a) niiSr^tiff. nmm:^itui tnmmMimjLX'^fj::5CRp\^p^7i^
0^9. -(^III(^CRP[^j^;CTPl3teS;5Sii;^fli-5^Jii5^^:)-^ u^'i^HK
mt^ 2 tfcft 5 c R p m^-^mmmt fj:^. ^tihummmim 1 . Runm
m^mtmibtitzt^. nmm^imR(D^^mK Bi^^Ltz^xhtut
25 ^nf±, AKDCRPWk&Xh'O, B 4 ^^Lfc#a-TfeH(^> A4jc:*5tt5C
y'^'^-y^mm^-o\^^xmmt^o ^5 (b) S'b^fit'^pjtfc^s (a
) mmm\^. m4i2it^*5tt5«^^^m^6<]{c^tfc^jo-c'fe5, (b)
wo 03/014740
PCT/JF02/08163
37
nmmmm i j-*3»t s^ftnicftAi-s ;i t t% ^©^^i^^^ss^o c r Pisis
10 'tl^. 5feSif(Z)CRP^SttB-p o i n t±-&.-^KJl±(D'(itT'fe5o
(^CRP(D^ft2)
hP-feryWp-;^|^tfjt^^CRP^^*:D^@^{btfc^m@atl5 1 ^
20 p^^F P^ Y't(Dm.-^w^^n\.tz.m^nm. ^-tt^^m^ p-^ h ^5^^
^SiS'p-^h^^^-i'^^jtfi^ ^W@^'fb^tifc^mil^{b;^i (5) . n
mmmtM (9) . ^mMimm (i4) ^tbj; u t)m^sM^^D
25 w ^titcmmxhm^m: 4 . ^»^s#Aia5 1 1 ^-^tf, . r (o^mi^ n
wo 03/014740
38
PCT/JP02/08163
^*1-ST r i s -Hc 1 mmm\^mmLX3omm'^t^m^it. 3 0
Tr i s-Hc \mmm§\mm^u 1 o^^mm'^Mzm'^tcikic,
glJOT r i s -HC 1 g»«W{rTH{c: 1 O^f^lM^pi^lliiD . )ji(7)»^tT '
K»C, ^CRPfet^fs:Fl:»P;iTic^>P^I8&if Lfc^tC, pH9<^)10%BSA
(4=iL?tT/v>^5 V) mm^mmi%i^^^Atzmn^xm^i-6z }ix\ mm
20000GT50 ^rm'b^mi-^ r i o L
^fitrm^mmm (i%bsa- vy^mm) '^immvtcm^. mm^
Xs 0. 8 fi m<D:7 ^ /U^ \zX'^T^Ltcm^. ^|J]©#='P-r KWfiO, 10
mm^ntcm^um^tt^m^mm^. m^o. 5 mmco s& p e t
wo 03/014740
PCT/JP02/08163
39
^W^nt UTEDTA • 2K^inx.fc:AWjfiL^^. y 5%
\z.ti: 5 J; 5 \zmn Lfco i (Oikm^Wi^m^cD C R P ^?^^APxl 5 i J;iJ; !? >
c) f*it>i-±OM^J^'a-<^S'J5fe
15 m (±jf[LCRP05£l:l) -CTOUfc^2!lilRi^j;iil5tLfeo ^(^-SlJ^!^*
M.^^&tLX. 0. Img/dK 0. Smg/dK 0. 6nig/
25 d K 1. Omg/d K 3. Omg/d K 6. Omg/d K 10. Omg
/d K 15. Omg/d U 20. Omg/dK 30. Omg/dlOCR
P ^'^^t^±5k^yU ^±y^\zmM Lxmm^ t^, #c r PiftS(^«
yto 6 3 5 nmt3:*5ttSS^3tS^thayL-C. ^CRPjg^lClSCTT'n 5/ h Lfc„
wo 03/014740
40
PCT/JP02/08163
-to ;tLe7°ns/ h^js, -msmmmMimi (s) t^bn^tift^^ms ^ii7°p
i:ftm@fe«III{:l*5V^T c R P {c*f1-^ u;^>K:x^>6SM7tt-5 :i ^:
A 1 ) <D?/.xh »9 . ^mAom^, ^mmmm i v^T c r psij;t;5s^jfe pt
mf£:iki)^i^^^^. m^B<Dm^^ ^yn-Mmmm^imi (bd ^tmm
CRPm&E(Dm^, C1~C3, D1~D3. E1~E3, 3^m±X(Dnm
mMa-^-h'y^'i-/utm(bti:6. ^(Dm-^. mmmmmi (ci. di. e
1) IX mi^ymy^^^^^ii,ich^^ti!)K nmm^imu (C2. D2. E2
25 ) ^ ^m^^mm (CS, D3, E-3) 55^P)i^^/•:^y^;6^fcSr ^:T':b*^5„ ^
tC, CRPIi^C, CRP«D, CRP^iSE{;:oV>Ti7ii-<5„ CRP^^C
■Ctt. 3;^7Blf^Td^biXi/-:^/V/6S^!9, /6*o^g5^^kSlJn (C 2) tl^^^jt
am (C3) Xii. *<^i^^/■:^yHc:^-^;^£^;asfc5,
m;g:fflV^•CCRP^ia$r|^^tl^tg•T?fc^„ CRP^SD. CRP«E^Cfc^t-5^
wo 03/014740
PCT/JP02/08163
41
^mMimn (d2, e2) Rimmmmimm (ds. es) oi^^i-Mt.
zx^m^mti-^^^) tj:m\ immmmmti^oiii^^iEm^. ^ytcRp
20 tLV^
wo 03/014740
42
PCT/JP02/08163
K^^^^fc0il^^L;t;is. ^mWs ^ytmWs mmv:. ^itm. mim
^bt^. **^lE^J^c*3v^T«. wK»;is-;^;^-r'fci9. ^mm<tmmm
10 MM^H^m^&mt LTtt. 7j<^7jc?ti^, itm. stm. ikm.
^^h^o ^fc, ffi^wii Lrc^tti5'^/N'i5^sr (CRP) ^MtLx^mm
(hCG) , Mi^TH/v^y (LH) , w^mmmts/u'&y, mmmf^t^j^^e
20 ^^tm. Bm^mmmmm. crp, ,mhu7f.z^^^, uhA
1 c, Tju-^^ymx-hi^hmmitfs:\^\ ^fc, Tka^s. ±«5}-iif.
M^5»m-e#s„ tfc, ^ii^^offl5i-c\ -efoi9?'^;5sP5^ -
wo 03/014740
43
PCT/JP02/08163
wo 03/014740
44
PCT/JP02/08163
©i*V LTV ^ S ,
■ mtdm.^(DnmmM^tm^m-f^^mii^^y^^-i-/\-ijii$xs:>^.
wo 03/014740
PCT/JP02/08163
45
^1 i i 1-5 /-^V
20 8. lf^(^)|5ffl^lmv^LW^O®llm7^0V^•ftL;6^e:|2^(D^^^;tir>'
wo 03/014740
PCT/JP02/08163
46
1 1 . ft^w^ism 1 1'^.tv ^ b|»^ W^H^ 1 0 3SOV ^■f ;h./54c:|a«c©^^'l' :t
:i i t-^ vi^o
10 12. it*(7?|£ffl^ 1 il?fev ^ Ln^(Dm^^ 1 1 «o V ^-f tL^b^^EicO/W ;f
1 3 . fs^oiEBB 1 ^j^djv N i.m^(Dmm^ 1 2 ^ov ^-f njaM^is^o/^-r :t
15 -fey1^(c*^v^x.
l^W. 0. 5mm~2. Onim-Cfe!9. $ ^tC, liitO^^ia^'fbWO^'l'
■ 14. it^o|iiSMl«^^v^Llt^o^H^l 3«ov^-r^^/5^^-ia«^(D''M;^-
25 15. fl*o«^l«?^^v^LW*©ra^l 4^Iov^Ttl;6>^^Ei^o/V:^-
1 6. it*W|EH^l^/^^^L|t^oOT^l 5^(DV^•ftb;6^c|E|fe<D/•^-f ;t
wo 03/014740
PCT/JP02/08163
15 :Lt^wmti-mm:}^mo
19. lt3jtw«£iS^l 73l*fcHit*(^^Hmi 83l{c:E«<^a'J:t;^fef-*5VN
20 r i: W <b -r 5
2 0 . mt.<Dmm^ tdm^ommf^ 1 9 v ^
2 1 . m^<Dmmm 1 7 ^?fev^ Lit*(Dmm 2 0 3Iov^■f n/^^iciiBicc^aij^
wo 03/014740
48
PCT/JP02/08163
:t± yt ^ffl V Nfciij^;^feT'fco T,
2 3 . mikomm^ i ? jij^^v ^ Lm^omm^ 2 2 ^m^-m7m^mn<DmM
10 ;^fi^c^5V^T.
15 :ffm^is\,^x.
wo 03/014740
PCT/JP02/08163
49
2 7 . W;^(n>mm%\-^-fi\^\Mi^(r>^% l o?!. i 2^/j^v^
15 fttiSK. A^o, 2#BS.t/3#@fc:Mi-s^ji@S«<^^fp;^;05|^--efe
2 9 . it3i^<z)®H^ 1 7 LH^o^fflU 2 6 3S(^)^^-f ti;6^Jc:|^<^IS)J;g
20 • tuW^S5t«/j5 3^mT'feS^
25
3 1. tt3ft<^OTm3 0IIlS«oa!IS:^fe(-*^v^-c,
wo 03/014740 PCT/JP02/08163
50
wo 03/014740
PCT/JP02/68163
^iEmmm<Dmm [2003^1^233(23. 01. 03) n^^i^^ss ■
te0i«*a)effl(4gEH/j L. (61) ]
10
20 a.
m^<Dmmmmmfmmx^h'o . mtm^^m^^mmi-^^^\zMLx. ±m
wo 03/014740 PCT/JP02/08163
52
wo 03/014740
53
PCT/JP02/08163
20 8. mrnd lf*w$allff lII'i:v^Uft5R<^»l^7II(75V^-ri^/JHc|^t^!i(7)^<
wo 03/014740
54
PCT/JP02/081fi3
10 12. ||*(D|Sia0 1 II/^V^ L||f*<7)|5ll^ 1 1 ^<D\^^-mii^^mm(Dy<^ :^
15 •fe>'f-{::fcv^T.
ymi)\ 0. 5inm~2. OmmT'^fJ, ^^(Dtmm^imm(Dy ^
20 ^t^mWLt't^y<'^ir'^>'^o
r i: ^^ <?: i- 5 / ^-r :t-tr
25 15. IS3jt(7)^|S|| 1 mi\^U%^(DmSiW> 1 4rlcoVN-ftL/j^{-Mc7)/M ;t
wo 03/014740
55
PCT/JP02/08163
18. (ffliEm) ^^w^m^mwi-r^mmm^m^s mmm^mm^mr^
15 ^t^o^ut-f-^m^iomo
25 ;ii:Sr#mi:-t-5«;^fe
wo 03/014740
56
PCT/JP02/08163
2 7. lt*oSellmlJI''J^V^U^*(7?|SE@^l OJI, fS?R(Dt5[l^l 2ri/djv%'
10 mmHmm^itm^3:bm-r:-h^.
15 ^:^;5Sftt)i^<, 75^0, 2#@^t>'3#B(ifig-r6t^||@^'ftgi50|i«:M(??]^fp
20 WfBK^S^fk^^isS;^/^^'^^,
25
3 1. l§*(^SaSla^3 03ll2«fe(75«:^^tCioV>T.
wo 03/014740
57
PCT/JP02/08163
m^^i 9^ (1) {zm^<Bmm
^mf)K h-y^t^m-r^. z-t^mm^Lito
15 (r>W^-fyiim—Qh^. z.k^mk^z.L.tz,
wo 03/014740
PCT/JP02/08163
wo 03/014740
PCT/JP02/08163
2/7
wo 03/014740
PCT/JP02/08163
3/7
1.000
ho
O
0.100
0. 010
o umm^im i
© @ ©
0 ©
o
•
• •
t
-t-
•
1
010 1.00 10.00 100.00
llifmmmM^W: \oe CRP (logmg/dl)
wo 03/014740
PCT/JP02/08163
CRPjiJg
wo 03/014740
PCT/JP02/08163
5/7
^6(3)^
wo 03/014740
PCT/JP02/08163
6/7
mm
0.010
0.10 1.00 10.00 100.00
^?S.^mM^^Sk log GRP (log-ms/dl)
wo 03/014740
PCT/JP02/08163
INTERNATIONAL SEARCH REPORT
Inremational application No.
PCT/JP02/08163
A. CLASSIFICATION OF SUBJECT MATTER
Int.Cl'' G01N33/543
According to International Patent Classification (IPC) or to both nationa] classification and IPC
B. FIELDS SEARCHED
Minimum documentation searched (classification system followed by classification symbols)
Int.Cl^ G01N33/543
Documentation searched other than minimum documentation to the extent that such documents are included in the fields searched
Jitsuyo Shinan Kbho 1922-1996 Toroku Jitsuyo Shinan Koho 1994-2002
Kbkai Jitsuyo Shinan Koho 1971-2002 Jitsuyo Shinan Toroku Kbho 1996-2002
Electronic data base consulted during the international search (name of data base and, where practicable, search terms used)
C. DOCUMENTS CONSIDERED TO BE RELEVANT
Category*
. Citation of document, with indication, where appropriate, of the relevant passages
Relevant to claim No.
X
JP 10-185921 A (Wakunaga Pharmaceutical Co., Ltd.)/
14 July, 1998 (14.07-98),
(Family: none)
1,2,4,5,
8-22,25-30
A
JP 8-278305 A (Nippon Shoji Kaisha, Ltd.),
22 October, 1996 (22.10.96),
(Family: none)
1-31
A
JP 11-326325 A (Dainippon Printing Co., Ltd.), ■
26 November, 1999 (26.11.99),
(Family: none)
1-31
A
JP 2000-46831 A (Bayer Corp.),
18 February, 2000 (18.02.00),
& EP 987551 A
^ 1-31
I [ Further documents are h'sted in the continuation of Box C. | [ See patent family annex.
♦ Special categories of cited documents: **V later document published after the international filing date or
"A" document defining the general state of the art which is not priority date and not in conflict with the application but cited to
considered to be of particular relevance understand the principle or theory underlying the invention
"E" earlier document but published on or after the international filing "X" document of particular relevance; the claimed invention cannot be
date considered novel or cannot be considered to involve an inventive
document which may throw doubts on priority claim(s) or which is step when the document is taken alone
cited to establish the publication date of another citation or other "Y^ document of particular relevance; the claimed invention cannot be
special reason (as specified) considered to involve an inventive step when the document is
"0^ document referring to an oral disclosure, use, exhibition or other combined with one or more other such documents, such
means combination being obvious to a person skilled in the art
*V document ptiblished prior to the international filing date but later document member of the same patent family
than the priority date claimed
Date of the actual completion of the international search
08 November, 2002 (08.11.02)
Date of mailing of the international search report
26 November, 2002 (26.11.02)
Name and mailing address of the ISA/
Japanese Patent Office
Facsimile No.
Authorized officer
Telephone No.
Form PCT/ISA/210 (second sheet) (July 1998)
ffl^^s#e m^mms'^ p ct/ j p o 2/0 s 1 e 3
A. ?sm(o&i-i>i^woi^m (ii§g#rF^« (i po )
Int. C 1 ' GO 1N3 3/543
Int. CI' GO INS 3/543
H*ffl*^?^^<&$8 1922-1996<¥
B:^m'&mmm^$^<d:m 1971-2002^
0*Hg®*ffltf^<i!t$B 1994-200 2^
H*ll*^^^^<ii:|R 1996-200 2<^
mm-r?>
X
JP 10-185921 A mikmmm^^m
1 9 9 8. 0 7. 1 4 (775 y-?ieU
1, 2, 4, 5, 8-
22. 25-30
A
JP 8-278305 A ( H «*:^S;^^±)
1 9 9 6. 1 0. 2 2 (77^
1-31
A
JP 11-326325 A (^0*MI*^#H:)
1 9 9 9. 1 1. 2 6 (775 y~^eU
1-31
(a*$:#t-)
r&j lR5-/^•xy h^r^y-XSt
0 8. 11. 0 2
25.11.02
B^H^fF/T (I SA/J P)
^{^#•§-1 0 0-8 9 1 5
mMa5=Pff:ffllK®;6S^HT i 4 § 3
03-3581-1101
2 J
9 0 15
3 2 5 0
«*:PCT/I SA/2 1 0 (m2-<-v?) (1 9 9 8^7^)
mmmm^^ pct/jpo2/o8 lea
A
JP 2 0 0 0-4 6 8 3 1 A (/W^/V=J— ^l^— v'a^')
2 0 0 0. 0 2. 1 8 &EP 9 8 7 5 5 1 A
1-31
«I^PCT/I SA/2 10 m2^-i^(r>m.^) (1 9 9 8^7^)
THIS PAGE BLANK (usPio)